Gene delivery systems can be divided into viral and non-viral systems. Non-viral gene delivery systems, based on “naked DNA” or formulated plasmid DNA, have potential benefits over viral vectors due to simplicity of use and lack of inciting a specific immune response. A number of synthetic gene delivery systems have been described to overcome the limitations of naked DNA, including cationic lipids, peptides, and polymers.
Polymers, on the other hand, have emerged as a viable alternative to current systems because of their excellent molecular flexibility allows for complex modifications and incorporation of novel chemistries. Cationic polymers, such as poly(L-lysine) (PLL) and poly(L-arginine) (PLA), polyethyleneimine (PEI) have been widely studied as gene delivery candidates due to their ability to condense DNA, and promote DNA stability and transmembrane delivery. The transfection efficiency of the cationic polymers is influenced by their molecular weight. Polymers of high molecular weight, e.g., greater than 20 kD, have better transfection efficiency than polymers of lower molecular weight. Polymers with high molecular weights, however, are more cytotoxic.
Poly(ethyleneimine) (PEI) condenses DNA into small narrowly distributed positively charged spherical complexes and can transfect cells in vitro and in vivo. PEI is similar to other cationic polymers in that the transfection activity of PEI increases with increasing polymer/DNA ratios. Commercial branched PEI is composed of 25% primary amines, 50% secondary amines and 25% tertiary amines.